Synaptotagmin-3 (Syt3) is a single-pass membrane protein of the synaptotagmin family with an N-terminal disulfide-forming cysteine motif and tandem cytoplasmic C2 domains. It is a high-affinity Ca2+ sensor: its C2 domains bind three Ca2+ ions and, in response to low micromolar Ca2+, bind anionic phospholipids (phosphatidylserine, PIP2) and t-SNARE complexes and stimulate SNARE-mediated membrane fusion. Unlike synaptotagmins 1 and 2, Syt3 is enriched in synaptic and other plasma membranes rather than on synaptic vesicles. Presynaptically it acts as the high-affinity Ca2+ sensor for synaptic vesicle replenishment and short-term plasticity; postsynaptically it binds GluA2 and drives activity-dependent AMPA receptor endocytosis, long-term depression and forgetting. It forms disulfide-linked homodimers and heterodimers with related synaptotagmins and is also expressed in endocrine cells, where it has been proposed to act as a plasma-membrane Ca2+ sensor for regulated exocytosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000149 SNARE binding | IBA GO_REF:0000033 | ACCEPT | Summary: Ca2+-promoted binding of Syt3 to t-SNARE heterodimers is inherited from the synaptotagmin ancestral node. Reason: The PAINT node covers the Ca2+-sensing synaptotagmins; rat Syt3 itself shows Ca2+-promoted syntaxin-1A/SNAP-25 binding (PMID:12860971, PMID:18508778), so it is inside the clade that kept this function. Supporting Evidence: PMID:12860971 Isoforms III, V, VII, and X exhibited robust Ca2+-promoted binding activity, whereas binding was much weaker or devoid for the other isoforms PMID:18508778 only the stimulatory syts I-III, V-VII, and IX-X bound t-SNAREs and PS in a Ca2+-promoted manner |
| GO:0000149 SNARE binding | IDA PMID:12860971 Identification of synaptotagmin effectors via acute inhibiti... | ACCEPT | Summary: Syt3 C2A shows robust Ca2+-promoted binding to purified SNAP-25/syntaxin heterodimers. Reason: Direct binding assay in the full text (Fig. 3); SNARE binding is part of the Syt3 Ca2+-sensor mechanism. Supporting Evidence: PMID:12860971 Isoforms III, V, VII, and X exhibited robust Ca2+-promoted binding activity, whereas binding was much weaker or devoid for the other isoforms |
| GO:0000149 SNARE binding | IDA PMID:18508778 Analysis of the synaptotagmin family during reconstituted me... | ACCEPT | Summary: The Syt3 cytoplasmic domain binds membrane-embedded t-SNAREs in a Ca2+-promoted manner in co-flotation assays. Reason: Full text read; Syt3 is among the stimulatory isoforms that bind t-SNAREs Ca2+-dependently. Supporting Evidence: PMID:18508778 only the stimulatory syts I-III, V-VII, and IX-X bound t-SNAREs and PS in a Ca2+-promoted manner PMID:18508778 In no case did a syt isoform stimulate fusion without binding to PS and t-SNAREs in a Ca2+-promoted manner |
| GO:0001786 phosphatidylserine binding | IDA PMID:12860971 Identification of synaptotagmin effectors via acute inhibiti... | ACCEPT | Summary: Syt3 C2A binds PS-containing liposomes. Reason: Full text shows C2A-III binds PS to the same extent as other C2A domains; PS binding is the membrane-penetration step of the Ca2+ sensor. Supporting Evidence: PMID:12860971 C2A-I and II failed to inhibit release by >10% despite the fact that both C2 domains bind PS to the same extent as the inhibitory C2A domains under the same conditions (e.g., C2A-III and -VII) |
| GO:0001786 phosphatidylserine binding | IDA PMID:18508778 Analysis of the synaptotagmin family during reconstituted me... | ACCEPT | Summary: Syt3 cytoplasmic domain binds PS-containing vesicles in a Ca2+-promoted manner. Reason: Co-flotation assays in the full text; Ca2+-promoted PS binding correlates with fusion stimulation. Supporting Evidence: PMID:18508778 only the stimulatory syts I-III, V-VII, and IX-X bound t-SNAREs and PS in a Ca2+-promoted manner PMID:18508778 In no case did a syt isoform stimulate fusion without binding to PS and t-SNAREs in a Ca2+-promoted manner |
| GO:0005509 calcium ion binding | TAS PMID:7791877 Ca(2+)-dependent and -independent activities of neural and n... | ACCEPT | Summary: Syt3 binds Ca2+ on its C2 domains (three ions per subunit). Reason: Calcium binding underlies its sensor activity; the TAS is consistent with curated UniProt cofactor data and Ca2+-dependent phospholipid binding assays. GO:0061891 calcium ion sensor activity is not an is_a descendant of calcium ion binding, so both terms stand. Supporting Evidence: UniProtKB:P40748 Binds 3 Ca(2+) ions per subunit PMID:7791877 The first C2 domains of Syt I, II, III, V and VII, but not of IV, VI or VIII, bind phospholipids |
| GO:0005515 protein binding | IPI PMID:30545844 Synaptotagmin-3 drives AMPA receptor endocytosis, depression... | MODIFY | Summary: Syt3 binds the AMPA receptor subunit GluA2 (Gria2); bare protein binding is uninformative. Reason: Per protein-binding policy, replace with the informative MF. The Syt3:GluA2 interaction is functionally important for AMPA receptor internalization (PMID:30545844). Proposed replacements: ionotropic glutamate receptor binding Supporting Evidence: PMID:30545844 Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting PMID:30545844 localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation |
| GO:0005515 protein binding | IPI PMID:9830048 Delineation of the oligomerization, AP-2 binding, and synpri... | MODIFY | Summary: Syt3 hetero-oligomerizes with Syt1 in a Ca2+-promoted manner via C2B; bare protein binding is uninformative. Reason: Per protein-binding policy, replace with the more informative heteromeric synaptotagmin interaction term already carried by the gene (GO:0046982). Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:9830048 Ca2+ promoted the hetero-oligomerization of synaptotagmin I with synaptotagmins III and IV UniProtKB:P40748 Can also form heterodimers with SYT6, SYT9 and SYT10 |
| GO:0005544 calcium-dependent phospholipid binding | IBA GO_REF:0000033 | ACCEPT | Summary: Ca2+-dependent phospholipid binding by C2A is an ancestral synaptotagmin function retained by Syt3. Reason: Rat Syt3 (RGD:3805) is among the donors with its own experimental evidence (PMID:7791877, PMID:11823420); this is expected, not circular. Supporting Evidence: PMID:7791877 The first C2 domains of Syt I, II, III, V and VII, but not of IV, VI or VIII, bind phospholipids PMID:11823420 the plasma membrane synaptotagmins 3 and 7 exhibited the highest Ca 2+ affinities |
| GO:0005544 calcium-dependent phospholipid binding | IDA PMID:7791877 Ca(2+)-dependent and -independent activities of neural and n... | ACCEPT | Summary: Syt3 C2A binds phospholipids Ca2+-dependently with EC50 in the low micromolar range. Reason: Core biochemical activity of the Ca2+ sensor. Supporting Evidence: PMID:7791877 The first C2 domains of Syt I, II, III, V and VII, but not of IV, VI or VIII, bind phospholipids PMID:11823420 the plasma membrane synaptotagmins 3 and 7 exhibited the highest Ca 2+ affinities |
| GO:0005544 calcium-dependent phospholipid binding | ISO GO_REF:0000121 | ACCEPT | Summary: Mouse Syt3 Ca2+-dependent phospholipid binding transfers to rat Syt3. Reason: Orthologous transfer consistent with direct rat data. Supporting Evidence: PMID:7791877 The first C2 domains of Syt I, II, III, V and VII, but not of IV, VI or VIII, bind phospholipids |
| GO:0005546 phosphatidylinositol-4,5-bisphosphate binding | IDA PMID:12860971 Identification of synaptotagmin effectors via acute inhibiti... | ACCEPT | Summary: Syt3 C2A binds PIP2-containing liposomes; inhibition of secretion by C2A domains correlated with PIP2 binding. Reason: Full text read; PIP2 binding is a recognised synaptotagmin effector interaction at the plasma membrane. Supporting Evidence: PMID:12860971 These results suggest that inhibitory domains affect release via interactions with PIP2 but not PS. |
| GO:0005768 endosome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Syt3 has been seen in endosomal compartments (multivesicular bodies in T cells; human GFP fusion). Reason: The human source is an IDA (LIFEdb GFP localisation) and mouse T-cell work places Syt3 in multivesicular bodies. Plausible but peripheral to its synaptic plasma membrane function. Supporting Evidence: PMID:17179206 it is mainly localized in multivesicular bodies |
| GO:0005886 plasma membrane | EXP PMID:11823420 Synaptotagmins form a hierarchy of exocytotic Ca(2+) sensors... | ACCEPT | Summary: Syt3 is a plasma membrane synaptotagmin in PC12 cells. Reason: Direct localization in the full text. Supporting Evidence: PMID:11823420 synaptotagmins 3 and 7, are also present on plasma membranes in PC12 cells PMID:10373432 synaptotagmin III is highly enriched in synaptic plasma membranes but not in synaptic vesicles |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane location is supported by direct rat data and the PAINT node. Reason: Rat Syt3 is a donor with its own evidence; consistent with synaptic plasma membrane enrichment. Supporting Evidence: PMID:11823420 synaptotagmins 3 and 7, are also present on plasma membranes in PC12 cells PMID:10373432 synaptotagmin III is highly enriched in synaptic plasma membranes but not in synaptic vesicles |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location Cell membrane maps to plasma membrane. Reason: Curated UniProt location with experimental evidence (PubMed:11823420). Supporting Evidence: PMID:11823420 synaptotagmins 3 and 7, are also present on plasma membranes in PC12 cells |
| GO:0007268 chemical synaptic transmission | IBA GO_REF:0000033 | ACCEPT | Summary: Syt3 participates in chemical synaptic transmission as a pre- and postsynaptic high-affinity Ca2+ sensor. Reason: Syt3 performs Ca2+-sensing steps in presynaptic vesicle replenishment and postsynaptic receptor endocytosis; the process term is as specific as the IBA node allows. Supporting Evidence: PMID:36261524 presynaptic high-affinity Ca2+ sensor, which drives vesicle replenishment and short-term synaptic plasticity PMID:30545844 localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Syt3 is a single-pass membrane protein of the plasma membrane; membrane is too general. Reason: Refine to plasma membrane, which the gene already carries with experimental support. Proposed replacements: plasma membrane Supporting Evidence: PMID:11823420 synaptotagmins 3 and 7, are also present on plasma membranes in PC12 cells PMID:10373432 synaptotagmin III is highly enriched in synaptic plasma membranes but not in synaptic vesicles |
| GO:0016079 synaptic vesicle exocytosis | TAS PMID:7791877 Ca(2+)-dependent and -independent activities of neural and n... | KEEP AS NON CORE | Summary: Syt3 is not a synaptic vesicle protein, but it acts presynaptically as a Ca2+ sensor for vesicle replenishment and priming. Reason: The 1995 TAS assumed a synaptic vesicle role by homology; Syt3 is excluded from synaptic vesicles (PMID:10373432) and is not the fast release sensor. Later knockout data place it in presynaptic vesicle replenishment, which is part of the synaptic vesicle exocytosis cycle, so the term is kept as non-core. Supporting Evidence: PMID:10373432 synaptotagmin III is highly enriched in synaptic plasma membranes but not in synaptic vesicles PMID:36261524 presynaptic high-affinity Ca2+ sensor, which drives vesicle replenishment and short-term synaptic plasticity file:rat/Syt3/Syt3-deep-research-manual.md Enriched in synaptic plasma membranes, not synaptic vesicles |
| GO:0016192 vesicle-mediated transport | IBA GO_REF:0000033 | MODIFY | Summary: Vesicle-mediated transport is true but general; Syt3 acts in Ca2+-regulated exocytosis and in Ca2+-triggered endocytosis of AMPA receptors. Reason: Refine to the specific descendants supported: calcium-ion regulated exocytosis (already on the gene) and endocytosis (receptor internalization at the postsynapse). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000001283 SUPPORTS TRANSFER Ancestral synaptotagmin node; claim transfers to rat Syt3, only granularity is refined. Proposed replacements: calcium-ion regulated exocytosis endocytosis Supporting Evidence: UniProtKB:P40748 Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain PMID:30545844 localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation |
| GO:0017156 calcium-ion regulated exocytosis | TAS PMID:7791877 Ca(2+)-dependent and -independent activities of neural and n... | ACCEPT | Summary: Syt3 is a Ca2+ sensor for Ca2+-regulated exocytosis. Reason: Supported by plasma-membrane sensor data in PC12 cells and in vitro fusion stimulation. Supporting Evidence: UniProtKB:P40748 Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain PMID:11823420 suggesting that these two synaptotagmins together serve as plasma membrane Ca 2+ sensors for exocytosis |
| GO:0017158 regulation of calcium ion-dependent exocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of Ca2+-dependent exocytosis is inherited from the synaptotagmin node; rat Syt3 is a donor. Reason: Consistent with Syt3 sensor function (PMID:11823420, PMID:18508778). Supporting Evidence: PMID:11823420 suggesting that these two synaptotagmins together serve as plasma membrane Ca 2+ sensors for exocytosis PMID:18508778 only the stimulatory syts I-III, V-VII, and IX-X bound t-SNAREs and PS in a Ca2+-promoted manner |
| GO:0017158 regulation of calcium ion-dependent exocytosis | IMP PMID:12860971 Identification of synaptotagmin effectors via acute inhibiti... | ACCEPT | Summary: Recombinant Syt3 C2A inhibited Ca2+-triggered exocytosis from cracked PC12 cells. Reason: Full text read. The assay is fragment interference and the same paper did not detect endogenous Syt3 in PC12 cells, so it tests competition with other syts rather than Syt3 loss; the claim itself is true for Syt3 (PMID:11823420, PMID:36261524) and is accepted, consistent with the IBA row. Supporting Evidence: PMID:12860971 Isoforms III, V, VII, and X exhibited robust Ca2+-promoted binding activity, whereas binding was much weaker or devoid for the other isoforms PMID:12860971 Syts III, IV, and VII were not detected at the level of sensitivity adequate for isoforms I and IX PMID:11823420 suggesting that these two synaptotagmins together serve as plasma membrane Ca 2+ sensors for exocytosis |
| GO:0030276 clathrin binding | IDA PMID:7791877 Ca(2+)-dependent and -independent activities of neural and n... | KEEP AS NON CORE | Summary: The Syt3 cytoplasmic region binds clathrin-AP2 with high affinity. Reason: Abstract-only; binding reported for all tested synaptotagmins and mostly reflects AP2 binding. Plausible link to the endocytic role but peripheral. Supporting Evidence: PMID:7791877 interacts with clathrin-AP2 (Kd = 0.1-1.0 nM) and with neural and non-neural syntaxins |
| GO:0030658 transport vesicle membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Syt3 is a plasma membrane protein, not an obligatory transport/secretory vesicle membrane protein. Reason: The UniProt secretory vesicle membrane location is ECO:0000305 (curator inference); rat brain fractionation excludes Syt3 from synaptic vesicles and PC12 data place it on the plasma membrane. Supporting Evidence: PMID:10373432 synaptotagmin III is highly enriched in synaptic plasma membranes but not in synaptic vesicles PMID:11823420 synaptotagmins 3 and 7, are also present on plasma membranes in PC12 cells |
| GO:0031340 positive regulation of vesicle fusion | IBA GO_REF:0000033 | ACCEPT | Summary: Positive regulation of vesicle fusion is placed on a Syt3 node with rat Syt3 as the experimental donor. Reason: The target appearing in its own WITH/FROM is expected; supported by direct reconstitution data. Supporting Evidence: PMID:18508778 only the stimulatory syts I-III, V-VII, and IX-X bound t-SNAREs and PS in a Ca2+-promoted manner |
| GO:0031340 positive regulation of vesicle fusion | IDA PMID:18508778 Analysis of the synaptotagmin family during reconstituted me... | ACCEPT | Summary: The Syt3 cytoplasmic domain stimulates SNARE-catalysed liposome fusion in response to Ca2+. Reason: Full text read; Syt3 is in the stimulatory class of isoforms. Supporting Evidence: PMID:18508778 only the stimulatory syts I-III, V-VII, and IX-X bound t-SNAREs and PS in a Ca2+-promoted manner PMID:18508778 In no case did a syt isoform stimulate fusion without binding to PS and t-SNAREs in a Ca2+-promoted manner |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | MODIFY | Summary: Syt3 forms disulfide-linked homodimers; identical protein binding is better captured as homodimerization. Reason: Refine to protein homodimerization activity, already on the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:99665 SUPPORTS TRANSFER Mouse Syt3 IPI/IDA self-association (PMID:10531343) transfers; only granularity refined. Proposed replacements: protein homodimerization activity Supporting Evidence: UniProtKB:P40748 Homodimer; disulfide-linked via the cysteine motif |
| GO:0042803 protein homodimerization activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Syt3 forms disulfide-linked homodimers via its N-terminal cysteine motif. Reason: Structural property; not the core sensor activity. Supporting Evidence: UniProtKB:P40748 Homodimer; disulfide-linked via the cysteine motif |
| GO:0046982 protein heterodimerization activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Syt3 heterodimerizes with SYT6, SYT9 and SYT10. Reason: Structural property; peripheral. Supporting Evidence: UniProtKB:P40748 Can also form heterodimers with SYT6, SYT9 and SYT10 |
| GO:0051592 response to calcium ion | IDA PMID:18508778 Analysis of the synaptotagmin family during reconstituted me... | MARK AS OVER ANNOTATED | Summary: The evidence is Ca2+ stimulation of in vitro liposome fusion, not a cellular response to calcium ion. Reason: Full text read. Response to calcium ion (a cellular/organismal response process) over-interprets an in vitro Ca2+ dependence that is already captured by calcium ion sensor activity and positive regulation of vesicle fusion. Supporting Evidence: PMID:18508778 only the stimulatory syts I-III, V-VII, and IX-X bound t-SNAREs and PS in a Ca2+-promoted manner |
| GO:0061891 calcium ion sensor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Syt3 is a high-affinity Ca2+ sensor. Reason: Core activity; Syt3 has among the highest Ca2+ affinities of the synaptotagmins and couples Ca2+ to fusion and endocytosis. Supporting Evidence: PMID:11823420 the plasma membrane synaptotagmins 3 and 7 exhibited the highest Ca 2+ affinities PMID:36261524 presynaptic high-affinity Ca2+ sensor, which drives vesicle replenishment and short-term synaptic plasticity |
| GO:0070382 exocytic vesicle | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Syt3 is excluded from synaptic vesicles and acts from the plasma membrane. Reason: The exocytic vesicle node reflects vesicular synaptotagmins (Syt1/2/9); Syt3 diverged in localization. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000001283 SUPPORTS SOURCE BUT NOT TARGET Vesicular synaptotagmins are on exocytic vesicles; Syt3 is a plasma membrane isoform. Supporting Evidence: PMID:10373432 synaptotagmin III is highly enriched in synaptic plasma membranes but not in synaptic vesicles PMID:11823420 synaptotagmins 3 and 7, are also present on plasma membranes in PC12 cells |
| GO:0097060 synaptic membrane | EXP PMID:10373432 The subcellular localizations of atypical synaptotagmins III... | ACCEPT | Summary: Syt3 is enriched in synaptic plasma membranes. Reason: Subcellular fractionation (abstract states it explicitly). Supporting Evidence: PMID:10373432 synaptotagmin III is highly enriched in synaptic plasma membranes but not in synaptic vesicles |
| GO:0097060 synaptic membrane | IDA PMID:10373432 The subcellular localizations of atypical synaptotagmins III... | ACCEPT | Summary: Immunocytochemistry shows Syt3 concentrated in synapses and synaptic plasma membranes. Reason: Consistent with other rows. Supporting Evidence: PMID:10373432 synaptotagmin III is concentrated in synapses, as expected PMID:10373432 synaptotagmin III is highly enriched in synaptic plasma membranes but not in synaptic vesicles |
| GO:0097060 synaptic membrane | IEP PMID:10373432 The subcellular localizations of atypical synaptotagmins III... | ACCEPT | Summary: Synaptic membrane location from the same study. Reason: IEP is used by SynGO-style curation for location; the location claim is sound. Supporting Evidence: PMID:10373432 synaptotagmin III is highly enriched in synaptic plasma membranes but not in synaptic vesicles |
| GO:0098793 presynapse | IEA GO_REF:0000108 | ACCEPT | Summary: Syt3 acts presynaptically. Reason: Supported by presynaptic knockout data (PMID:36261524) and synaptic enrichment. Supporting Evidence: PMID:36261524 presynaptic high-affinity Ca2+ sensor, which drives vesicle replenishment and short-term synaptic plasticity PMID:10373432 synaptotagmin III is concentrated in synapses, as expected |
| GO:0098794 postsynapse | ISO GO_REF:0000121 | ACCEPT | Summary: Syt3 localizes to postsynaptic endocytic zones. Reason: Mouse SynGO IDA (PMID:30545844) transfers to rat. Supporting Evidence: PMID:30545844 localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation |
| GO:0099072 regulation of postsynaptic membrane neurotransmitter receptor levels | ISO GO_REF:0000121 | ACCEPT | Summary: Syt3 Ca2+-sensing drives AMPA receptor internalization, regulating postsynaptic receptor levels. Reason: Mouse IDA/IMP (PMID:30545844); Syt3 itself performs the Ca2+-sensing and GluA2 binding step of receptor removal. Supporting Evidence: PMID:30545844 localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation PMID:30545844 Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting |
| GO:1903861 positive regulation of dendrite extension | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: The human source concerns melanocyte dendrite elongation in an overexpression screen of C2 domains; melanocyte dendrites are not neuronal dendrites. Reason: GO:0030425 dendrite is defined as a neuron projection, so positive regulation of dendrite extension mis-scopes the melanocyte phenotype, which is in any case overexpression evidence. The ISO propagation carries that term into rat. Propagation Review Root cause: SOURCE BAD Failure modes: CONTEXT OR TISSUE MISMATCH SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q9BQG1 SOURCE WEAK OR INFERRED Human UniProt IDA from PMID:23999003 (abstract focused on SYT14L; C2-domain overexpression screen in melanocytes). Supporting Evidence: PMID:23999003 Sixteen sets of C2 domain-containing proteins were identified whose over-expression resulted in dendrite lengthening |
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Download this section (compressed HTML)Q: Should SynGO/RGD record Syt3 presynaptic function in vesicle replenishment with a priming/docking term (e.g. GO:0016082 synaptic vesicle priming) once direct mechanistic (not only knockout) evidence exists?
Q: Is the human SYT3 annotation to positive regulation of dendrite extension (melanocyte, PMID:23999003) appropriate given that GO dendrite is restricted to neurons?
Experiment: Test whether Syt3 C2B Ca2+-binding mutants rescue fast vesicle replenishment in Syt3 knockout synapses, and whether Syt3 directly promotes tight docking in reconstituted docking assays.
Experiment: Map the Syt3-GluA2 binding interface and test whether Syt3 recruits AP2/clathrin directly to drive receptor endocytosis in a Ca2+-dependent manner.
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